Angela Filoni

Prevalence of specific anti-skin autoantibodies in a cohort of patients with inherited epidermolysis bullosa

BackgroundInherited epidermolysis bullosa (EB) is a group of skin diseases characterized by blistering of the skin and mucous membranes.There are four major types of EB (EB simplex, junctional EB, dystrophic EB and Kindler syndrome) caused by different gene mutations. Dystrophic EB is derived from mutations in the type VII collagen gene (COL7A1), encoding a protein which is the predominant component of the anchoring fibrils at the dermal-epidermal junction.For the first time in literature, we have evaluated the presence of anti-skin autoantibodies in a wider cohort of patients suffering from inherited EB and ascertained whether they may be a marker of disease activity.MethodsSera from patients with inherited EB, 17 with recessive dystrophic EB (RDEB), 10 with EB simplex (EBS) were analysed. As much as 20 patients with pemphigus vulgaris, 21 patients with bullous pemphigoid and 20 healthy subjects were used as controls.Anti-skin autoantibodies were tested in all samples with the Indirect Immunofluorescence (IIF) method and the currently available ELISA method in order to detect anti-type VII collagen, anti-BP180 and anti-BP230 autoantibodies.ResultsThe mean concentrations of anti-type VII collagen autoantibodies titres, anti-BP180 and anti-BP230 autoantibodies were statistically higher in RDEB patients than in EBS patients.The sensitivity and specificity of the anti-type VII collagen ELISA test were 88.2% and 96.7%. The Birmingham Epidermolysis Bullosa Severity score, which is used to evaluate the severity of the disease, correlated with anti-skin autoantibodies titres.ConclusionsThe precise pathogenic role of circulating anti-skin autoantibodies in RDEB is unclear. There is a higher prevalence of both anti-type VII collagen and other autoantibodies in patients with RDEB, but their presence can be interpreted as an epiphenomenon.

Vitamin D and Atopic Dermatitis in Childhood

Vitamin D features immunomodulatory effects on both the innate and adaptive immune systems, which may explain the growing evidence connecting vitamin D to allergic diseases. A wealth of studies describing a beneficial effect of vitamin D on atopic dermatitis (AD) prevalence and severity are known. However, observations linking high vitamin D levels to an increased risk of developing AD have also been published, effectively creating a controversy. In this paper, we review the existing literature on the association between AD and vitamin D levels, focusing on childhood. As of today, the role of vitamin D in AD is far from clear; additional studies are particularly needed in order to confirm the promising therapeutic role of vitamin D supplementation in childhood AD.

Effectiveness of etanercept in children with plaque psoriasis in real practice: a one-year multicenter retrospective study

Abstract Background: Etanercept is licensed for the treatment of moderate-to-severe plaque psoriasis in children. Objectives: The aim of this analysis was to investigate effectiveness, tolerability, and reasons for discontinuation of etanercept in a real-life cohort of children and adolescents with moderate to severe plaque psoriasis. Methods: Data collected from a number of centers belonging to the ‘Pediatric Dermatology Group’ of the Italian Society of Dermatology (SIDeMaST) were examined in patients (age ≤17 years) who started treatment with etanercept from 2011 to 2015. A group of 23 patients were identified. Efficacy assessment was defined as the proportion of patients with a ≥50% and ≥75% improvement in Psoriasis Area Severity Index (PASI) at weeks 12, 24, and 52. Safety was evaluated on adverse event reporting. Reasons for discontinuation were classified as ineffectiveness, adverse events, remission, or other reasons. Results: At week 12, 56.5% of patients achieved PASI 75, 86.9% achieved PASI 50. Efficacy was sustained through week 52. In 15 patients etanercept was still ongoing at the time of data collection. In three patients the therapy was suspended due to inefficacy. The medication was overall well tolerated. Conclusions: Etanercept was an effective and well-tolerated treatment in this real-life cohort of patients.

Classic and HIV-related Kaposi sarcoma treated with 0.1% topical timolol gel

T cells, or CD56 NK cells expressing NKG2D. We collected blood samples 4 times, and the FACS analysis was also performed by dividing into 4 times. Therefore, final data were represented as a fold change of each cells expressing NKG2D over the healthy control (control set to 1). The patients were segregated into 2 or 3 subgroups according to AA severity, activity, type, and treatment modalities for subgroup analysis. Statistical analysis was performed using the ManneWhitney U test and KruskaleWallis analysis. Double-labeling immunofluorescence microscopy in 2 representative cases using freshly frozen specimens was also performed. The results showed that the levels of NKG2DCD8 T cells and NKG2DCD56 NK cells were higher in the AA group compared with the control group (P \ .05). Interestingly, a 2.49-fold increase in the CD4 T cells subset expressing NKG2D was detected in the peripheral blood from patients with AA compared with healthy controls (P \ .05; Fig 1). Although not statistically significant, the proportion of NKG2DCD4 T cells was lower in patients who had mild severity AA and in those who received systemic immunosuppressive therapy. Double label immunofluorescence revealed NKG2D cells coexpressed CD4 around the hair follicles of the AA lesion (Fig 2). Recently, the role of NKG2DCD4 T cells in other chronic autoimmune diseases, such as Crohn’s disease and rheumatoid arthritis, was highlighted. A subset of CD4 T cells expressing NKG2D was higher in the lamina propria of patients with Crohn’s disease. These NKG2DCD4 T cell clones were functionally active through major histocompatibility complex class I-related chain A (MICA) eNKG2D interactions, producing IFNand killing targets expressing MICA. We hypothesize that NKG2DCD4 T cells might exhibit a TH1 cytokine profile in patients with AA. Our results suggest that IFNeproducing NKG2DCD4 T cells have the potential to become therapeutic targets and biologic markers of disease activity in AA. However, additional studies are needed to characterize the functional properties of NKG2DCD4 T cells in patients with AA.

Cutaneous Infections from Aquatic Environments

The onset of various skin infestations can be observed after exposure to microbial agents present in aquatic environments. Infection by Mycobacterium marinum, that lives in salt- and freshwater, generally follows minor trauma of the hands when carrying out aquarium maintenance activities, and can give rise to a single nodular lesion or sporotrichoid forms, featuring several nodules running along the lymphatic drainage lines. Multiple or disseminated lesions are observed in subjects with an immune deficiency. Infection by Mycobacterium ulcerans most frequently affects children in Africa, South-East Asia, Latin America, and Oceania. The complaint presents with one or more subcutaneous indolent nodules that slowly evolve to ulcers and ultimately to very disabling scars. Some rapidly growing mycobacteria, that can also be present in domestic water, can cause abscesses or nodules that evolve to ulcers. Erysipeloid mainly affects the hands, and is reported in fishermen, butchers and housewives: it presents as a dark, erythematous, raised area with an irregular, centrifugal extension and distinct margins, sometimes together with generalized symptoms. Wounds from any causes may become infected by various microorganisms; in particular, Vibrio vulnificus is highly virulent and can be the cause of gastroenteritis or invasive septicemia after eating raw or undercooked shellfish, as well as necrotizing wound infections following marine injuries. These pose a high risk of fatality. Pseudomonas dermatitis follows after exposure to contaminated water in heated swimming pools, whirlpools, hot tubes, and also during a shower/bath.

Scalp hair heterochromia in a 5-year-old child: rare somatic mosaicism?

Scalp hair heterochromia presenting in tufts with no underlying skin changes is rare and can be a sign of somatic mosaicism. We describe the case of a healthy 5‐year‐old boy with this condition.

Eyelid milia en plaque: a treatment challenge with a new CO2 fractional laser.

Milia en plaque (MEP) is an uncommon finding characterized by numerous tiny milia within an erythematous area.

Tobacco-induced contact dermatitis

Tobacco and tobacco smoke are strongly associated with various skin conditions, among which contact dermatitis is of prime importance. The aetiological and clinical aspects vary according to the different tobacco production and processing steps. Contact dermatitis is frequent in tobacco harvesters, curers and cigar makers, whereas it rarely affects smokers and, only exceptionally, cigarette packaging workers. The skin sites involved also vary, according to whether the exposure is occupational or non-occupational. Tobacco contact irritation is far more frequent than contact allergy. The sensitizing compound in tobacco is unknown; nicotine, while highly toxic, does not seem to cause sensitization, except in rare cases. Besides natural substances, several compounds are added to tobacco during processing and manufacturing. For this reason, identifying the aetiological factors is exceedingly difficult. Another important aspect to take into account is the co-causative role of tobacco in eliciting or exacerbating contact dermatitis in response to other agents, occupational or extra-occupational.

Dermatitis caused by Coelenterates

The phylum of Coelenterata (Cnidaria), animals that have a worldwide distribution, includes four toxic classes: Anthozoa (sea anemones, true hard and soft corals and sea pens), Scyphozoa (true jellyfish), Hydrozoa (physalia and fire corals: not true corals), and Cubozoa (box jellyfish). Highly specialized cells (nematocytes) are present on the surface of Coelenterata, and associated with the venom discharged during stings. An organ synthesized by the nematocytes, the nematocyst, is expelled in a harpoon-like fashion during a nanosecond process, and injects different active toxic substances into the prey. Injuries caused by cnidarians are of two pathogenic orders, toxic (the most common mechanism) and allergic (of immediate or delayed type). Different clinical pictures can arise after Cnidarians envenomations, featuring skin and systemic reactions that can even be fatal. True jellyfish induce a great number of accidents in the world, although they are generally less severe than those caused by box jellyfish and physaliae. Box jellyfish are among the most significant toxic marine animals, and their envenomation usually presents as a medical emergency. Sea anemones can cause cutaneous and systemic manifestations, including seabather’s eruption, characterized by pruriginous papulous lesions that persist for 1–4 weeks. True corals provoke skin lesions through toxic and traumatic mechanisms. Physaliae stings are usually painful and severe, and go together with systemic manifestations that can involve various organs. Reactions to fire corals are also very severe. A correct diagnosis and appropriate treatment are essential in cases of cnidarian envenomations, particularly because specific antivenoms are lacking.

Cost Analysis of a Novel Enzymatic Debriding Agent for Management of Burn Wounds

Introduction. Given its efficacy and safety, NexoBrid™ (NXB) has become part of our therapeutic options in burns treatment with satisfactory results. However, no cost analysis comparing NXB to the standard of care (SOC) has been carried out as of today. Aim. To assess the cost of treatment with NXB and compare it to the SOC cost. Methods. 20 patients with 14–22% of TBSA with an intermediate-deep thermal burn related injury were retrospectively and consecutively included. 10 of these patients were treated with the SOC, while the other 10 with NXB. The cost analysis was performed in accordance with the weighted average Italian Health Ministry DRGs and with Conferenza Stato/Regioni 2003 and the study by Tan et al. For each cost, 95% confidence intervals have been evaluated. Results. Considering the 10 patients treated with NXB, the overall savings (total net saving) amounted to 53300 euros. The confidence interval analysis confirmed the savings. Discussion. As shown by our preliminary results, significant savings are obtained with the use of NXB. The limit of our study is that it is based on Italian health care costs and assesses a relative small cohort of patients. Further studies on larger multinational cohorts are warranted.